Cerebellar Ataxia

Cerebellar Ataxia

Sidney Shemanski

SPA 220 01

Assignment 4a

December 6, 2021
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The cerebellum which is Latin for “little brain” is a lobe located on the dorsal side of the

brain inferior to the occipital and temporal lobes. It is divided into 2 hemispheres and 3 separate

lobes and is connected to the medulla oblongata, pons, and midbrain by the inferior, middle, and

superior peduncles.1 The three lobes are the anterior lobe, posterior lobe, and the flocculonodular

lobe. The primary fissure separates anterior and posterior lobe while the posterolateral fissure

separates the flocculonodular lobe from the posterior lobe. The two hemispheres are connected

by a narrow strip of tissue which is known as the vermis, associated with posture and movement

of the body. The cerebellum is composed of white and gray matter mimicking the cerebrum. The

cortex is made up of gray matter and differs from the cerebrum due to there being three different

layers.2 There is an outer layer made up of axons and dendrites, a middle layer made up of

purkinje cells, and an inner layer made up of small granule cells.2 The inner white matter is

known as the “arbor vitae” because of its tree-like branched appearance. The white matter is

composed of the folia, gyri, and deep nuclei. The deep nuclei are the most important part of the

cerebellum associated with its function of motor control. There are 4 paired main nuclei.3 The

dentate nuclei (largest and most lateral), emboliform nuclei, globose nuclei, and fastigial nuclei

(most medial).3 These nuclei all receive input from different regions from the cerebellar cortex

and are responsible for different actions.4

The main function of the cerebellum is connected to the maintenance of balance and

posture; coordination of voluntary movements; motor learning; and cognitive functions.3

Through vestibular receptors and proprioceptors, the cerebellum regulates the commands to

motor neurons to direct certain body positions or different focuses in muscles.3 It mainly focuses

on how many muscle groups act upon one action, so it's crucial for the cerebellum to coordinate

the timing and force of each muscle in every situation. 2 Somatotopic maps of anterior and
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posterior lobes are associated with proximal and distal musculature, while the vermis and

paravermal cortex are closely connected with spinal, vestibular and brainstem areas controlling

balance, muscles, eye movements, and gait.3 A “sequencing hypothesis” states that the

cerebellum uses past experiences of spatial and temporal relationships and uses it to predict

future outcomes.5 It then compares the predicted outcome to the actual outcome and if it does not

align, then the cerebellum adjusts it’s output to the cortex accordingly. 4 Even though the

cerebellum is known for coordination and control of movement, recent research has shown that it

also plays a role in emotional and cognitive function as well. 3 Personality change, mood

disorder, psychiatric disorders such as schizophrenia, and ADHD have been questioned as

connecting to the deformity of the cerebellum. 3

Cerebellar ataxia is one of the most commonly known neurological disorders affecting

the cerebellum.5 Ataxia is a disorder that results in impaired speech, uncoordinated limb

movements, and impaired balance: all functions that are controlled by the cerebellum.1

Cerebellar ataxia occurs due to lesions in the cerebellum.1 Different areas of lesions affect

different functions of motor control. Lesions in the midline area (fastigial deep nucleus) of the

cerebellum cause deficits in posture, locomotions, and oculomotor control.1 Lesions in the

globose and emboliform deep nucleus results in limb tremor and limb impairments.1 Lesions in

the dentate deep nucleus then result in poor visuomotor coordination, fine-control of voluntary

movement, cognition, and language.1 Dyssynergia, uncoordinated and abrupt movements, is also

a very common result in ataxia. This results from the inability for movement-associated

interaction torques. Meaning that one movement of a joint cannot successfully cause another

movement of a joint.1 Resulting in simpler, more accurate single joint movements.1 Tremor is one

sign that is gained in ataxia due to the lack of control of the muscles. Because of the single joint
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movements, muscle activation of alternating agonists and antagonists is present. Tremor at rest is

not seen in cerebellar dysfunction, however tremor is visible while maintaining posture and

while moving (kinetic tremor).1

When diagnosed with ataxia, the motor dysfunction is caused by the degeneration of

neurons in the cerebellum and all of its pathways.5 Purkinje cells are neurons specifically in the

cerebellum and they project to the deep cerebellar nuclei. They are very easily recognizable due

to their largely branched, flat, dendrites and have a single long axon. Due to the Purkinje neurons

connecting the cerebellar cortex to the deep cerebellar nuclei, they have an important role in

motor function.4 They regulate motor coordination by receiving complicated inputs from parallel

fibers and integrating them into a signal.4 The Purkinje cells then send information that gets

routed to the ventrolateral nucleus of the thalamus via the deep cerebellar nuclei.4 The thalamus,

which is known as the “relay center” then sends those motor signals to the cerebral cortex of the

brain.4 Dysfunction of these Purkinje neurons have a huge affect on how efficient the cerebellum

can control balance, posture, and walking, and coordination by causing cerebellar ataxia.

Recent studies have shown that neuronal dysfunction results from mutations in specific

ion-channels that regulate membrane excitability.5 Ion channel dysfunction can be directly related

to motor dysfunction and degeneration of neurons in ataxia.5 These purkinje neurons are

dependent on precise, coordinated activity of ion-channels to control the activity of the neurons.5

In order to properly send motor information, Purkinje neurons must be able to fire rapidly and

precisely.5 Without precise activity of ion channels, spontaneous action potentials will occur due

to sodium carried by voltage gated sodium channels.5 The voltage gated sodium channels cause

the action potential, while the falling phase of the action potential is caused by voltage gated

potassium channels.5 Upon depolarization however, voltage gated calcium channels become
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activated which allow calcium entry into purkinje neurons.5 This calcium entry then has an effect

on the function of the purkinje cells and must be consistent to regulate the voltage gated calcium

channels.5 Without these channels being precise, the Purkinje neurons will not be able to

effectively act as an output for cerebellar motor processing.5 When there are ion channel

mutations or simply just ion channel dysfunction, the Purkinje neurons will not work properly

which leads to ataxia.5 Dysfunction and even death of purkinje cells synapse on the dentate

nucleus which results in the degeneration of the dentate nucleus and furthermore results in

cerebellar ataxia.5

There is no known cure for cerebellar ataxia, however there are many treatments such as

therapy or medications that help improve the severity of it. One common treatment for cerebellar

ataxia is the medication, Riluzole.6 It has several actions such as blocking excitatory amino acid

receptors, inhibiting glutamate release, inactivation of voltage-dependent sodium channels, and

stimulating G-protein dependent signal transduction.6 It is not certain, however, hypothesized

that riluzole activates calcium-dependent potassium channels.6 This allows inhibition of deep

cerebellar nuclei and decreases cerebellar hyperexcitability.6 In a case study, 39 participants were

evaluated over an 8-week period when treated with riluzole. The International Cooperative

Ataxia Rating Scale was used to measure kinetic and static motor control as well slurred speech.6

On this 100 point scale, the patients decreased 5 points and showed improvement in those

measurements of motor control.6 Another type of treatment would be different therapeutic tactics.

Even though physical therapy for cerebellar ataxia is largely unknown, it is widely used to help

control the movements of the body that are impaired.6 There are many different therapies such as

physical, occupational, and speech therapy that have shown to improve ataxia symptoms through

a systematic review done by allied health care.6

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References
1. Marsden J, Harris C. Cerebellar ataxia: pathophysiology and rehabilitation. Clin Rehabil.
2011;25(3):195-216.doi: http://dx.doi.org/10.1177/0269215510382495
2. Morgan O, Slapik M, Iannuzzelli K, etg al. The cerebellum and implicit sequencing:
evidence from cerebellar ataxia. 2021;20(2):222-245. doi:10.1007/s12311-020-01206-7
3. Gowen E, Miall RC. The cerebellum and motor dysfunction in neuropsychiatric
disorders. Cerebellum. 2007;6(3):268-279. doi:10.1080/14734220601184821
4. Das J, Leon A. Neuroanatomy, dentate nucleus. In: StatPearls [Internet]. Publishing:
2021. Accessed December 2, 2021. https://www.ncbi.nlm.nih.gov/books/NBK554381/
5. Bushart DD, Shakkottai VG. Ion channel dysfunction in cerebellar ataxia. Neurosci Lett.
2019;688:41-48. doi:10.1016/j.neulet.2018.02.005
6. Sarva H, Shanker VL. Treatment options in degenerative cerebellar ataxia: a systematic
review. Mov Disord Clin Pract. 2014;1(4):291-298. doi:10.1002/mdc3.12057